Gas fermentation is an upcoming technology utilizing autotrophic microorganisms to convert gaseous feedstock into products of higher value. As a key element, the envisioned “autotrophic biorefinery” incorporates CO2/CO as an alternative carbon source aiming to establish decarbonization of the energy and material sector. However, besides its high potential, gas fermentation comes up with several new challenges. Gas fermentations are characterized by limited substrate solubility, and thus, low mass transfer. This chapter summarizes potential feedstocks and products as well as different types of microbial cultures employed for bioconversion. It discusses applicable reactor configurations to enhance gas transfer from gas to liquid phase and, finally, presents various approaches and upcoming techniques, for example, electrofermentation, to overcome specific barriers of this highly promising bioconversion concept.